Psychiatric morbidity after screening for breast cancer.
One hundred and thirty two women with normal breast screening results were interviewed six months after their attendance at the Edinburgh Breast Screening Clinic. Eight percent of women said screening had made them more anxious about developing breast cancer. Thirty eight percent said they were more aware of the disease since screening but they regarded this as advantageous. Seventy percent of the women were still practising breast self-examination. There was no difference in the psychiatric morbidity of the screened sample when compared with a matched random sample community control group. Neither was there any difference in the General Health Questionnaire case rates before and after screening. Screening does not appear to increase the prevalence of psychiatric morbidity. Twenty nine percent of the interview sample were examining their breasts more than once a month--21% once a week or more. However, these frequent self-examiners did not have a greater prevalence of psychiatric morbidity than their matched controls.


Suboptimal use of neural information in a mammalian auditory system.
Establishing neural determinants of psychophysical performance requires both behavioral and neurophysiological metrics amenable to correlative analyses. It is often assumed that organisms use neural information optimally, such that any information available in a neural code that could improve behavioral performance is used. Studies have shown that detection of amplitude-modulated (AM) auditory tones by humans is correlated to neural synchrony thresholds, as recorded in rabbit at the level of the inferior colliculus, the first level of the ascending auditory pathway where neurons are tuned to AM stimuli. Behavioral thresholds in rabbit, however, are ∼10 dB higher (i.e., 3 times less sensitive) than in humans, and are better correlated to rate-based than temporal coding schemes in the auditory midbrain. The behavioral and physiological results shown here illustrate an unexpected, suboptimal utilization of available neural information that could provide new insights into the mechanisms that link neuronal function to behavior.


Timing of mother-to-child transmission of HIV-1 and infant mortality in the first 6 months of life in Harare, Zimbabwe.
To examine the risks of intra-uterine (IU), intra- and early post-partum (IP/ePP) and late post-partum (LPP) mother-to-child transmission (MTCT) of HIV-1 and infant mortality in the first 6 months of life. Whole blood was collected in ethylenediaminetetra-acetic acid at birth, 6 weeks, 3 and 6 months from 996 infants born to HIV-1 seropositive mothers. Polymerase chain reaction using Roche DNA amplification assay, version 1.5 (Roche Diagnostics Incorporation, Alameda, California, USA) was used to determine timing of MTCT. Logistic regression models determined risk factors for HIV-1 transmission and survival analyses examined mortality by timing of transmission. Two hundred and forty-nine mothers (30.7%) transmitted HIV-1 infection to their infants by 6 months of age. Eighty-nine infants [9.4%; 95% confidence interval (CI), 7.7-11.5], 104 infants (16.0%; 95% CI, 10.8-21.2) and 21 infants (5.3%; 95% CI, 1.6-12.2) were infected IU, IP/ePP and LPP respectively. Low maternal CD4 cell count and arm circumference were risk factors for IP/ePP transmission. Infant mortality was higher among infected infants than uninfected (P < 0.001, log rank test). Timing of infection, birth weight and maternal CD4 cell counts were important factors in predicting infant death. In the first 6 months of life, IU and IP/ePP transmission contributed more than three-quarters of the 30.7% MTCT. Our data, in addition to serving as a historical comparison, may be useful in designing and evaluating the efficacy of short course antiretroviral trials aimed at reducing MTCT in developing countries.


Risk of Fracture During Androgen Deprivation Therapy Among Patients With Prostate Cancer: A Systematic Review and Meta-Analysis of Cohort Studies.
Background: Androgen deprivation therapy (ADT) suppresses the production of androgen, and ADT is broadly used for intermediate or higher risk disease including advanced and metastatic cancer. ADT is associated with numerous adverse effects derived from the pharmacological properties. Previous meta-analysis on fracture risk among ADT users possessed limited data without further subgroup analysis. Risk estimation of updated real-world evidence on ADT-related fracture remains unknown. Objectives: To assess the risk of fracture and fracture requiring hospitalization associated with ADT among prostate cancer population on different disease conditions, treatment regimen, dosage level, fracture sites. Methods: The Cochrane Library, PubMed, and Embase databases were systematically screened for eligible cohort studies published from inception to March 2020. Two authors independently reviewed all the included studies. The risks of any fracture and of fracture requiring hospitalization were assessed using a random-effects model, following by leave-one-out, stratified, and sensitivity analyses. The Grading of Recommendations Assessments, Development and Evaluations (GRADE) system was used to grade the certainty of evidence. Results: Sixteen eligible studies were included, and total population was 519,168 men. ADT use is associated with increasing fracture risk (OR, 1.39; 95% CI, 1.26-1.52) and fracture requiring hospitalization (OR, 1.55; 95% CI, 1.29-1.88). Stratified analysis revealed that high-dose ADT results in an elevated risk of fracture with little statistical heterogeneity, whereas sensitivity analysis restricted to adjust for additional factors indicated increased fracture risks for patients with unknown stage prostate cancer or with no restriction on age with minimal heterogeneity. The GRADE level of evidence was moderate for any fracture and low for fracture requiring hospitalization. Conclusion: Cumulative evidence supports the association of elevated fracture risk with ADT among patients with prostate cancer, including those with different disease conditions, treatment regimens, dose levels, and fracture sites. Further prospective trials with intact information on potential risk factors on fracture under ADT use are warranted to identify the risky population.


Transformable H-bonds and conformation in compressed glucose.
In response to external stimuli the α-d-glucose molecule extensively transforms its H-bonding pattern and conformation. High-pressure reverses the linear compressibility and changes the hierarchy of intermolecular interactions in crystalline α-d-glucose. At 5.40(2) GPa it undergoes an isostructural phase transition rearranging the OH···O hydrogen bonds, promoting the role of CH···O contacts and eliminating voids in the structure. Such monotonic and abrupt transformations may be characteristic of sugars and polysaccharides.


Use of PCR to identify enteroaggregative Escherichia coli as an important cause of acute diarrhoea among children living in Calcutta, India.
The importance of enteroaggregative Escherichia coli (EAggEC) as a possible aetiological agent of acute diarrhoea among children in Calcutta, India, was investigated. Simultaneously the use of a previously described PCR diagnostic system was assessed for its ability to identify EAggEC infection. E. coli strains isolated during a 1-year case-control study from faecal samples of 388 children aged <5 years, with or without diarrhoea, were examined for EAggEC by HeLa cell adherence assay in parallel with a PCR assay with primers generated from an EAggEC DNA probe. A blind comparison was made between the two methods to determine their diagnostic potential. E. coli isolates that adhered to HeLa cells in an aggregative pattern were the sole isolates significantly more often in 254 cases (9%) than in 134 control (2%) children. Age stratification showed that EAggEC were isolated more frequently from children aged <36 months. The EAggEC isolates belonged to several O serogroups and showed multiple drug resistance. Both methods were positive for 26 samples, nine samples were positive by PCR alone and seven samples were positive by culture alone, thus indicating a 78% sensitivity and 97% specificity for the PCR assay. EAggEC is an important aetiological agent of acute diarrhoea among infants in and around Calcutta, and the PCR diagnostic system may be useful to identify such infection in epidemiological studies.


Matched groups analysis method.
The matched group analysis method in prospective studies is a variation of matched pairs analysis with the advantage of sampling error avoided in the choosing of pairs of subjects. An example is shown in which comparisons are given of mortality in triads of cases classified by the tar and nicotine level of the cigarettes they smoked and matched on 10 variables. The method can also be used in retrospective and autopsy studies.


[Mutagenic action of acenaphthene on haploid and diploid cultures of Candida scottii].
Acenaphthene used as vapour increases the frequency of morphological mutations as well as mutations yielding strains with a reduced activity of respiration in Candida scottii. The diploid culture has more mutants than the haploid culture. The frequency of mutants depends on the duration of acenaphthene action. Cells more resistant to the action of acenaphthene vapour are selected in the haploid culture when C. scottii cells are transferred many times into new wort drops. As a result, the frequency of mutations decreases. When the diploid culture is exposed to the action of acenaphthene vapour for a longer time, the frequency of mutations rises. Apparently, the diploid culture has a lower activity of reparation of premutational damages than the haploid culture and therefore the number of mutant cells increases.


Rapid Single-Cell Microbiological Analysis: Toward Precision Management of Infections and Dysbiosis.
Bacterial infection is a leading cause of morbidity and mortality (from infants to the elderly) and accounts for more than $20 billion in healthcare costs in the United States each year. The pathogens responsible for many of the common infectious diseases, such as urinary tract infection (UTI) and ventilator-associated infections (VAIs), have proven to be highly adept in acquiring mechanisms of antimicrobial resistance. The use of broad-spectrum antibiotics by healthcare providers and the infiltration of antibiotics in the environment have accelerated the selection and growth of resistant pathogens. To further exacerbate the problem, the need for new antibiotics has far outpaced the development of new classes of antibiotics by the pharmaceutical industry (only two new classes of antibiotics have reached the market in the last 20 years), in large part due to prohibitive cost and historically poor return on investment to develop new antibiotics. Consequently, clinicians have limited treatment options, particularly in the neediest patients. To tackle this major global health issue, we are developing novel technological approaches for rapid definitive clinical microbiological analysis. These technologies will improve the clinical management of bacterial infections and reduce the improper use of antibiotics in current practice, hopefully limiting the spread of drug-resistant organisms.


Analysis of interferograms from a diffractive-lens-based common-path interferometer.
We present a method of numerical analysis of interferograms for a diffractive-lens-based common-path interferometer recently introduced by Elfström et al. [Opt. Express 14, 3847 (2006)OPEXFF1094-408710.1364/OE.14.003847]. Practical aspects such as the effect of higher diffraction orders upon the interferograms are considered. We show that this method can be used to solve the phase function of the inspected lens. In addition, we show that by using this method it is possible to estimate the focal length and imaging properties of the inspected lens.


Testosterone improves muscle fiber asset and exercise performance in a metabolic syndrome model.
Lifestyle modifications, including physical exercise (PhyEx), are well-known treatments for metabolic syndrome (MetS), a cluster of metabolic and cardiovascular risk factors often associated to hypogonadism. Given the trophic role of testosterone on skeletal muscle (SkM), this study was aimed at evaluating the effects of testosterone treatment on SkM metabolism and exercise performance in male rabbits with high-fat diet (HFD)-induced MetS. HFD rabbits, treated or not with testosterone (30 mg/kg/week) for 12 weeks, were compared to regular diet animals (RD). A subset of each group was exercise-trained for 12 weeks. HFD increased type-II (fast, glycolytic) and decreased type-I (slow, oxidative) muscle fibers compared to RD as evaluated by RT-PCR and histochemistry. Testosterone reverted these effects, also inducing the expression of mitochondrial respiration enzymes and normalizing HFD-induced mitochondrial cristae reduction. Moreover, testosterone significantly increased the expression of myogenic/differentiation markers and genes related to glucidic/lipid metabolism. At the end of the PhyEx protocol, when compared to RD, HFD rabbits showed a significant reduction of running distance and running time, while testosterone counteracted this effect, also decreasing lactate production. In the trained groups, muscle histology showed a significant reduction of oxidative fibers in HFD compared to RD and the positive effect of testosterone in maintaining oxidative metabolism, as also demonstrated by analyzing mitochondrial ultrastructure, succinate dehydrogenase activity and ATP production. Our results indicate that testosterone could be useful to promote oxidative muscle metabolism altered by MetS, thus improving exercise performance. Conversely, testosterone administration to otherwise eugonadal rabbits (RD) only increased muscle fiber diameter but not endurance performance.


Nasopharyngeal mature teratoma in the newborn.
Teratomas which originate from two or three germ layers are the most common congenital tumors of the childhood and are usually observed in the sacrococcygeal region. The nasopharynx is a considerably rare localization. Nazopharyngeal tumors may lead to significant findings including apnea, respiratory distress and stridor in newborns. In this study, a female newborn who developed respiratory distress minutes after cesarean delivery was presented. Examination following a difficult intubation and radiological examination revealed presence of a nasopharyngeal mass in the baby who was born at the 30(th) gestational age from a 30-year old primipar woman. The nasopharyngeal mass was excised and histopathological examination revealed mature teratoma. Although nasopharyngeal teratoma is a benign tumor, it may lead to urgency of airway management in the newborn. In this case presentation, the differential diagnosis and treatment of nasopharyngeal teratoma was discussed in accompaniment with the literature information.


Treatment of BRONJ with ozone/oxygen therapy and debridement with piezoelectric surgery.
Bisphosphonate related osteonecrosis of the jaw (BRONJ) is progressive bone destruction in the maxillofacial region of patients under current or previous treatment with Bisphosphonates. The present case series study aimed to evaluate if ozone/oxygen therapy and debridement with piezoelectric surgery may improve the treatment of BRONJ. The treatment modality of the patients included ozone/oxygen mixture from medical oxygen. The protocol for ozone/oxygen mixture therapy appointments was set as twice a week for 10 weeks, for a total of 20 applications for each patient. The evaluation of the lesions was based on the clinical and radiologic parameters. The primary outcome was the necrotic lesion reduction during ozone/oxygen therapy sessions and up to the end of follow up periods. The healing of the lesion was taken as a positive result. The level of significance was taken as p <0.05. A total of 14 patients affected by osteonecrosis were included. The mean follow-up of the patients was 14.3 months. The overall success rate after treatment was 64.2%. According to the results, ozone/oxygen therapy and debridement with Piezoelectric surgery for BRONJ treatment is a safe procedure with successful outcomes.


Microgeographic population genetic structure in the northern water snake, Nerodia sipedon sipedon detected using microsatellite DNA loci.
We describe the isolation and genetic characterization of eight microsatellite DNA loci from the northern water snake, Nerodia sipedon sipedon and use these loci to analyse levels of genetic differentiation between local (< 2 km apart) populations of these snakes in Ontario. These loci are variable, with expected heterozygosities ranging from 0.28 to 0.91, and can correctly exclude nonsires in parentage analyses with a high probability (0.998). Population analyses reveal significant deviation from expected heterozygosity levels for one population, probably a result of a null allele(s) at a single locus and small but significant levels of genetic differentiation among all three populations. This demonstrates that microgeographic genetic structure exists in this species, possibly due to limited dispersal.


Palliative Care and Care Partner Support in Neuro-oncology.
The journey for a patient with a brain tumor and their loved ones can be extremely challenging due to the high burden of physical symptoms and the emotional distress caused by the diagnosis. Optimizing quality of life by addressing symptoms and reducing this emotional distress can improve treatment tolerance and outcomes and alleviate care partner distress and burden. Symptoms in patients with central nervous system (CNS) tumors can vary in onset and intensity, ranging from headaches, seizures, and focal weakness to emotional distress and cognitive dysfunction. Additionally, care partners may demonstrate distress due to the high burden of care and need appropriate support structures and access to resources to alleviate this stress. Evidence-based recommendations are unfortunately limited given the lack of high-quality research in this area, but patients living with CNS tumors and their loved ones can benefit from early and routine symptom identification and management, compassionate and transparent communication, and practical guidance for the future. These principles are part of palliative care, a field of medicine focused on alleviating suffering in patients with serious, chronic illness. Clinicians involved in the care of patients with CNS tumors must be educated in these important primary palliative care principles. This article focuses on key symptom management, strategies for high-quality communication, a discussion of advance care planning, and an overview of end-of-life care.


Dynamic Risk Prediction of 30-Day Mortality in Patients With Advanced Lung Cancer: Comparing Five Machine Learning Approaches.
Administering systemic anticancer treatment (SACT) to patients near death can negatively affect their health-related quality of life. Late SACT administrations should be avoided in these cases. Machine learning techniques could be used to build decision support tools leveraging registry data for clinicians to limit late SACT administration. Patients with advanced lung cancer who were treated at the Department of Oncology, Aalborg University Hospital and died between 2010 and 2019 were included (N = 2,368). Diagnoses, treatments, biochemical data, and histopathologic results were used to train predictive models of 30-day mortality using logistic regression with elastic net penalty, random forest, gradient tree boosting, multilayer perceptron, and long short-term memory network. The importance of the variables and the clinical utility of the models were evaluated. The random forest and gradient tree boosting models outperformed other models, whereas the artificial neural network-based models underperformed. Adding summary variables had a modest effect on performance with an increase in average precision from 0.500 to 0.505 and from 0.498 to 0.509 for the gradient tree boosting and random forest models, respectively. Biochemical results alone contained most of the information with a limited degradation of the performances when fitting models with only these variables. The utility analysis showed that by applying a simple threshold to the predicted risk of 30-day mortality, 40% of late SACT administrations could have been prevented at the cost of 2% of patients stopping their treatment 90 days before death. This study demonstrates the potential of a decision support tool to limit late SACT administration in patients with cancer. Further work is warranted to refine the model, build an easy-to-use prototype, and conduct a prospective validation study.


Intestinal parasites in Kampuchea, Takeo Province.
Fresh stool samples obtained from 1407 adult patients who sought treatment in Takeo province hospital and 332 Takeo preschool and school-age children from 3 to 18 years of age were examined for the presence of intestinal parasites using the technique of native preparation and the flotation method of Faust with subsequent staining with Lugol solution to demonstrate cysts. In hospital patients, a total of 13 protozoan and 9 helminth species were diagnosed. The prevalence of Entamoeba histolytica (cysts and trophozoites) was highest in the age group 15-18 years (18.3%), the peak prevalence of Gairdia lamblia (27.6%) occurred in children of the age group 6-9 years. The highest frequency distribution of Pentatrichomonas hominis (20.1%) was recorded in 3 to 5 years old, that of Enteromonas hominis (12.8%) in 6 to 9 years old. The predominant helminth was Ancylostoma duodenale, with the peak prevalence (65.2%) in patients older than 18 years, followed by Ascaris lumbricoides and Strongyloides stercoralis. Almost half of children patients under 6 was infected with at least two species of parasites, patients over 6 were infected simultaneously with two or more intestinal parasites in an absolute majority of cases. In Takeo preschool and school children the spectrum of diagnosed protozoan and helminth species was somewhat narrower than seen in hospital patients, but their prevalence rates were higher, except for the flagellate Pentatrichomonas hominis. The highest prevalence rates recorded were for E. histolytica 29.5% (age category 10-14 years), for G. lamblia 34.8% (age category 6-9 years), for P. hominis 19.3% (age category 3-5 years), for E. hominis 10.5% (age category 3-5 years), for A. duodenale 85.9% (age category 15-18 years), for A. lumbricoides 26.1% (age category 6-9 years), and for S. stercoralis 18.8% (age category 6-9 years). As many as 70% of children at the age between 6 and 15 years were simultaneously infected with two or three species of intestinal parasites.


Identification of putative insect brush border membrane-binding molecules specific to Bacillus thuringiensis delta-endotoxin by protein blot analysis.
Binding sites for insecticidal toxins of Bacillus thuringiensis are located in the brush border membranes of insect midguts. Two approaches were used to investigate the interactions of B. thuringiensis subsp. kurstaki HD-73 CryIA(c) toxin with brush border membrane vesicles from sensitive and naturally resistant insects: 125I-toxin-vesicle binding assays and protein blots probed with 125I-CryIA(c) toxin. In bioassays, Manduca sexta and Heliothis virescens larvae were highly sensitive, Helicoverpa zea larvae were moderately sensitive, and Spodoptera frugiperda larvae were resistant to CryIA(c) toxin. Studies of binding of 125I-CryIA(c) toxin to brush border membrane vesicles from the larval midguts revealed that all insects tested had high-affinity, saturable binding sites. Significantly, S. frugiperda larvae bind but are not killed by CryIA(c) toxin. Labeled CryIA(c) toxin incubated with protein blots identifies a major binding molecule of 120 kDa for M. sexta and 148 kDa for S. frugiperda. H. virescens and H. zea are more complex, containing 155-, 120-, 103-, 90-, and 63-kDa proteins as putative toxin-binding molecules. H. virescens also contains a minor toxin-binding protein of 81 kDa. These experiments provide information that can be applied toward a more detailed characterization of B. thuringiensis toxin-binding proteins.


The role of endothelial-mesenchymal transition in heterotopic ossification.
Heterotopic ossification (HO) is a process by which bone forms in soft tissues, in response to injury, inflammation, or genetic disease. This usually occurs by initial cartilage formation, followed by endochondral ossification. A rare disease called fibrodysplasia ossificans progressiva (FOP) allows this mechanism to be induced by a combination of genetic mutation and acute inflammatory responses. FOP patients experience progressive HO throughout their lifetime and form an ectopic skeleton. Recent studies on FOP have suggested that heterotopic cartilage and bone is of endothelial origin. Vascular endothelial cells differentiate into skeletal cells through a mesenchymal stem cell intermediate that is generated by endothelial-mesenchymal transition (EndMT). Local inflammatory signals and/or other changes in the tissue microenvironment mediate the differentiation of endothelial-derived mesenchymal stem cells into chondrocytes and osteoblasts to induce HO. We discuss the current evidence for the endothelial contribution to heterotopic bone formation.


Aromatic pathways in carbathiaporphyrins.
Magnetically induced current densities and current pathways have been calculated for carbaporphyrins and carbathiaporphyrins using the gauge including magnetically induced current (GIMIC) method. The aromatic character and current pathways are obtained from the calculated current density susceptibilities. The current-density calculations show that five of the studied carbaporphyrinoids are aromatic, two are antiaromatic, and one is nonaromatic. The analysis of the current pathways of the investigated molecules reveals some general trends for the current flow in carbaporphyrinoids. Insertion of a CH2 group into the all-carbon ring generally cuts or restricts the current flow, leading to a stronger current of the alternative pathway of the ring. No obvious trends regarding the current strengths and pathways of the thiophene and cyclopentadienyl rings were obtained. The present study shows that it is indeed difficult to predict the electron delocalization pathways of general carbaporphyrinoids. Thus, a careful analysis of the current density is necessary for determining their electron delocalization pathways.


[Correlation of the nitrate and ascorbic acid content in vegetables and fruits].
Comparison of the evidence on the content of nitrates and ascorbic acid in vegetables and fruits shows that the content of ascorbic acid in fruits exceeds that of nitrates whereas in a number of vegetables the nitrate content is greater than that of ascorbic acid. With increase in the amount of nitrogen fertilizers introduced, the content of nitrates in vegetables grows more intensively as compared to ascorbic acid. The range of these variations is relative to the type and grade of vegetables. During the storage of beet and cabbage the decreased content of ascorbic acid correlated well with the amount of nitrogen-containing mineral fertilizers introduced. It is recommended that fruits and berries be used first of all as a source of ascorbic acid, while rhubarb, fall radish and salad be restricted in the diet.


Antifertility actions of alpha-chlorohydrin in the male.
Non-steroidal chemicals that affect male fertility have been known for over 25 years but only one compound, alpha-chlorohydrin, possesses most of the attributes of an ideal male contraceptive. In the male rat, for example, continuous daily oral administration of low doses produces an almost immediate and continuous antifertility response that ceases when treatment is withdrawn. Such a dose regime does not interfere with libido, is apparently not toxic and the action is specific towards mature sperm. Furthermore, the action of the compound is species-specific: it is effective in the rat, ram, boar, guinea pig, hamster, rhesus monkey and upon ejaculated human sperm but it is ineffective in the mouse and the rabbit. High doses of alpha-chlorohydrin can be neurotoxic, nephrotoxic and, in rats, lead to prolonged or permanent infertility. However, the antifertility response and the toxicity of racemic alpha-chlorohydrin may be due, respectively, to the separate enantiomers. No other antifertility chemical has been investigated to such an extent as alpha-chlorohydrin; this article reviews the progress that has been achieved with alpha-chlorohydrin during the past six years.


mRNA levels can be reduced by antisense oligonucleotides via no-go decay pathway.
Antisense technology can reduce gene expression via the RNase H1 or RISC pathways and can increase gene expression through modulation of splicing or translation. Here, we demonstrate that antisense oligonucleotides (ASOs) can reduce mRNA levels by acting through the no-go decay pathway. Phosphorothioate ASOs fully modified with 2'-O-methoxyethyl decreased mRNA levels when targeted to coding regions of mRNAs in a translation-dependent, RNase H1-independent manner. The ASOs that activated this decay pathway hybridized near the 3' end of the coding regions. Although some ASOs induced nonsense-mediated decay, others reduced mRNA levels through the no-go decay pathway, since depletion of PELO/HBS1L, proteins required for no-go decay pathway activity, decreased the activities of these ASOs. ASO length and chemical modification influenced the efficacy of these reagents. This non-gapmer ASO-induced mRNA reduction was observed for different transcripts and in different cell lines. Thus, our study identifies a new mechanism by which mRNAs can be degraded using ASOs, adding a new antisense approach to modulation of gene expression. It also helps explain why some fully modified ASOs cause RNA target to be reduced despite being unable to serve as substrates for RNase H1.


Liver resections can be performed safely without Pringle maneuver: A prospective study.
To evaluate liver resections without Pringle maneuver, i.e., clamping of the portal triad. Between 9/2002 and 7/2013, 175 consecutive liver resections (n = 101 major anatomical and n = 74 large atypical > 5 cm) without Pringle maneuver were performed in 127 patients (143 surgeries). Accompanying, 37 wedge resections (specimens < 5 cm) and 43 radiofrequency ablations were performed. Preoperative volumetric calculation of the liver remnant preceeded all anatomical resections. The liver parenchyma was dissected by water-jet. The median central venous pressure was 4 mmHg (range: 5-14). Data was collected prospectively. The median age of patients was 60 years (range: 16-85). Preoperative chemotherapy was used in 70 cases (49.0%). Liver cirrhosis was present in 6.3%, and liver steatosis of ≥ 10% in 28.0%. Blood loss was median 400 mL (range 50-5000 mL). Perioperative blood transfusions were given in 22/143 procedures (15%). The median weight of anatomically resected liver specimens was 525 g (range: 51-1850 g). One patient died postoperatively. Biliary leakages (n = 5) were treated conservatively. Temporary liver failure occurred in two patients. Major liver resections without Pringle maneuver are feasible and safe. The avoidance of liver inflow clamping might reduce liver damage and failure, and shorten the hospital stay.


Human MPS1 kinase is required for mitotic arrest induced by the loss of CENP-E from kinetochores.
We have determined that the previously identified dual-specificity protein kinase TTK is the human orthologue of the yeast MPS1 kinase. Yeast MPS1 (monopolar spindle) is required for spindle pole duplication and the spindle checkpoint. Consistent with the recently identified vertebrate MPS1 homologues, we found that hMPS1 is localized to centrosomes and kinetochores. In addition, hMPS1 is part of a growing list of kinetochore proteins that are localized to nuclear pores. hMPS1 is required by cells to arrest in mitosis in response to spindle defects and kinetochore defects resulting from the loss of the kinesin-like protein, CENP-E. The pattern of kinetochore localization of hMPS1 in CENP-E defective cells suggests that their interaction with the kinetochore is sensitive to microtubule occupancy rather than kinetochore tension. hMPS1 is required for MAD1, MAD2 but not hBUB1, hBUBR1 and hROD to bind to kinetochores. We localized the kinetochore targeting domain in hMPS1 and found that it can abrogate the mitotic checkpoint in a dominant negative manner. Last, hMPS1 was found to associate with the anaphase promoting complex, thus raising the possibility that its checkpoint functions extend beyond the kinetochore.


Influence of spirituality and religiousness on substance misuse in patients with schizophrenia or schizo-affective disorder.
Substance misuse represents a major issue in the treatment of schizophrenia patients. Spirituality and religiousness have been shown to reduce substance misuse and to foster recovery among substance misusers in the general population. One hundred and fifteen stabilized outpatients with schizophrenia (mean age 39; 70% male) were selected in 2004 for an interview about religious coping. Religious involvement was significantly inversely correlated to substance use and abuse. A content analysis showed that religion may play a protective role toward substance misuse in 14% of the total sample, especially for patients who had stopped substance misuse (42%). It played a negative role in 3% of cases. Religion may play a role in the recovery of schizophrenia patients with substance misuse comorbidity.


[Extra-focal instrumental fixation of the spine in the surgical treatment of tuberculous spondylitis].
The complex procedure for treating tuberculous spondylitis involving a short-term (1-2 months) antibacterial therapy and early functional resection of the diseased vertebral bodies with defect replacement by an autograft and extra-focal fixation of the resected spinal portion by Byzov's apparatus applied in 492 patients proved to be highly efficacious. The reliable apparatus fixation of the spinal zone operated on allows early (on day 7) activation of patients which promotes functional normalization of organs and systems, activation of reparative processes, shortening of treatment duration and reduction of disabled cases. Clinical and X-ray findings show that a bone block formed 4-6 months after surgery and 67% of the patients finished their therapy during a year. Introduction of the procedure into the treatment of spinal injuries and diseases will be of the socioeconomical value.


Further studies on the melanophores of periodic albino mutant of Xenopus laevis.
It is still unknown why dermal melanophores disappear during larval development, and why no or very few epidermal melanophores appear during and after metamorphosis, in Xenopus laevis showing periodic albinism (ap). To elucidate these points, we investigated the occurrence of depigmentation in mutant (ap/ap) melanophores during in vitro proliferation and the incidence of melanophore differentiation from mutant melanoblasts in the skin in vitro. During in vitro proliferation of mutant melanophores, ap-type melanosomes decreased in number gradually and instead the number of premelanosomes increased in the cells, which caused depigmentation at the light microscopic level in the culture. Depigmentation was observed only in mutant melanophores, and not in wild-type (+/+) melanophores. These results suggest that autonomous depigmentation of mutant dermal melanophores is the cause of the disappearance of these cells in vivo. Dopa-positive melanoblasts were demonstrated in both wild-type and mutant skins. However, the melanoblasts of metamorphosed mutant froglets did not differentiate in vitro, while those of wild-type froglets did. These results suggest that mutant melanoblasts in the skin of froglets lose the potency to differentiate into melanophores, and that this causes the lack of mutant melanophores in the froglets. The site of action of the ap gene is also discussed.


Preparation and evaluation of poly(lactic-co-glycolic acid) microparticles as a carrier for pulmonary delivery of recombinant human interleukin-2: II. In vitro studies on aerodynamic properties of dry powder inhaler formulations.
The aim of this study was the preparation and evaluation of dry powder formulations of recombinant human interleukin-2 (rhIL-2)-loaded microparticles to be administered to the lung by inhalation. As indicated in our previous study, the microparticles were prepared by modified water-in-oil-in-water (w(1)/o/w(3)) double emulsion solvent extraction method using poly(lactic-co-glycolic acid) (PLGA) polymers. The dry powder formulations were prepared with blending of microparticles and mannitol as a coarse carrier. The actual aerodynamic characteristics of the microparticles alone and prepared mixtures with mannitol are evaluated by using the eight-stage Andersen cascade impactor. Due to the low tapped density of microparticles (<0.4 g/cm(3)), the theoretical aerodynamic diameter (MMADt) values were calculated (<5 μm) on the basis of the geometrical particle diameter and tapped density values. The lowest tapped density value (0.17 g/cm(3)) belongs to the cyclodextrin-containing formulation. According to the results obtained using the cascade impactor, the emitted doses for all microparticle formulations were found to be rather high and during the aerosolization for all the formulations except F3 and F5, >90% of the capsule content was determined to be released. However, the actual aerodynamic diameter (MMADa) values were seen to be higher than the MMADt values. The blending of the microparticles with mannitol allowed their aerodynamic diameters to decrease and their fine particle fraction values to increase. The obtained results have shown that the mixing of rhIL-2-loaded microparticles with mannitol possess suitable aerodynamic characteristics to be administered to the lungs by inhalation.


[Dynamic renal scintigraphy in assessing kidney function in patients with nonspecific colitis].
Research into the morphofunctional status of the kidneys was conducted in patients with nonspecific colitis-NC (nonspecific ulcerative colitis-NUC and Crohn's disease). Urodynamics and partial function of the kidneys were assessed in 74 NC patients (51 NUC patients and 23 patients with Crohn's disease) on the basis of the findings of two-nuclide dynamic renal scintigraphy with 131I-hippuran and 99mTc-pentatech. Despite the absence of clinical symptomatology of urinary tract lesions, marked dysfunction of the kidneys of various degree (depending on severity of disease, tactics of its treatment and a type of surgical intervention) was noted in NC patients. In most cases changes of renal function were without visible clinical manifestations and were frequently undetectable by routine laboratory tests. Therefore dynamic renal scintigraphy was found necessary for investigation on NC patients.


Four studies on how past and current suicidality relate even when "everything but the kitchen sink" is covaried.
T. E. Joiner's (2004, in press) theory of suicidal behavior suggests that past suicidal behavior plays an important role in future suicidality. However, the mechanism by which this risk is transferred and the causal implications have not been well studied. The current study provides evaluation of the nature and limits of this relationship across 4 populations, with varying degrees of suicidal behavior. Across settings, age groups, and impairment levels, the association between past suicidal behavior and current suicidal symptoms held, even when controlling for strong covariates like hopelessness and symptoms of various Axis I and II syndromes. Results provide additional support for the importance of past suicidality as a substantive risk factor for later suicidal behavior.


A case report of steroid resistant cardiac sarcoidosis successfully managed with methotrexate.
Up to one fourth of sarcoidosis patients may have cardiac involvement, what is potentially a life-threatening condition and requires aggressive treatment. Corticosteroids are generally effective in cardiac sarcoidosis, however may have significant short and long term adverse effects. We present a case of a 42-year-old male, who was diagnosed with pulmonary and cardiac sarcoidosis. He was treated initially with corticosteroids and satisfactory improvement was achieved in the lungs but not in the heart. Methotrexate was added as a second line therapy, being beneficial for the heart as well as steroid sparing agent. Cardiac improvement was documented during serial CMR imaging. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 178-181).


Concentrations and fate of decamethylcyclopentasiloxane (D(5)) in the atmosphere.
Decamethylcyclopentasiloxane (D(5)) is a volatile compound used in personal care products that is released to the atmosphere in large quantities. Although D(5) is currently under consideration for regulation, there have been no field investigations of its atmospheric fate. We employed a recently developed, quality assured method to measure D(5) concentration in ambient air at a rural site in Sweden. The samples were collected with daily resolution between January and June 2009. The D(5) concentration ranged from 0.3 to 9 ng m(-3), which is 1-3 orders of magnitude lower than previous reports. The measured data were compared with D(5) concentrations predicted using an atmospheric circulation model that included both OH radical and D(5) chemistry. The model was parametrized using emissions estimates and physical chemical properties determined in laboratory experiments. There was good agreement between the measured and modeled D(5) concentrations. The results show that D(5) is clearly subject to long-range atmospheric transport, but that it is also effectively removed from the atmosphere via phototransformation. Atmospheric deposition has little influence on the atmospheric fate. The good agreement between the model predictions and the field observations indicates that there is a good understanding of the major factors governing D(5) concentrations in the atmosphere.


Self-rated mental health in socio-structural contexts: an examination with Korean American older adults.
Following the socio-structural framework of health, the study examined the role of social/interpersonal and environmental/neighborhood factors in predicting self-rated mental health (SRMH) in Korean American older adults. Using the survey data from 420 older Korean Americans (mean age = 71.6, SD = 7.59), multivariate models of SRMH was estimated with sets of predictors: (1) background information (demographic characteristics and chronic conditions), (2) mental health symptom measures (depressive symptoms and anxiety), (3) social/interpersonal factors (social network and filial satisfaction), and (4) environmental/neighborhood factors (neighborhood safety and residential satisfaction). Social/interpersonal and environmental/neighborhood factors were found to make a significant contribution to the predictive model even after controlling for background information and mental health symptom measures. Those with higher levels of filial satisfaction and more favorable perceptions of neighborhood safety were likely to have positive ratings of SRMH. Findings supported the importance of considering socio-structural contexts in the assessment of SRMH and provided implications for mental health services for the target population.


Regulation of guinea pig ileal electrolyte transport by M3-muscarinic acetylcholine receptors in vitro.
To determine the muscarinic receptor subtype mediating guinea pig ileal mucosal electrolyte secretion, we compared the potencies (Kb) of selective M1 (pirenzepine) (PZ), M2 (AF-DX 116, methoctramine), and M3 [4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP), hexahydrosiladifenidol (HHSiD)] antagonists as inhibitors of carbachol-induced reductions in guinea pig atrial heart rate and ileal longitudinal muscle contractions, responses mediated by M2 and M3 receptors, respectively. Pretreatment with all five muscarinic antagonists shifted the carbachol concentration-response curve to the right, in a manner suggesting competitive antagonism. The following affinity profiles (Kb, nM) were obtained for: 1) ileal mucosa: 4-DAMP (2.7) greater than HHSiD (23.0) greater than PZ (110) greater than or equal to methoctramine (395) greater than AF-DX 116 (784); 2) atrial heart rate: 4-DAMP (9.5) congruent to methoctramine (11) greater than AF-DX 116 (63) greater than HHSiD (222) greater than PZ (256); and 3) ileal longitudinal muscle: 4-DAMP (3.1) greater than HHSiD (21) greater than PZ (143) greater than methoctramine (388) greater than or equal to AF-DX 116 (482). The selectivity profiles of these antagonists suggest that muscarinic receptors in the ileal mucosa more closely resemble those in the ileal muscle (M3) than those in atrial muscle (M2). Moreover, M1-muscarinic receptors appear to be relatively unimportant in mediating the effects of carbachol on short circuit current (ISC). Carbachol-induced increases in ISC were also unaffected by pretreatment with 0.5 microM tetrodotoxin, suggesting that electrolyte transport in the guinea pig ileal mucosa may be mediated, in part, by postsynaptic M3-muscarinic receptors on the enterocytes.


The effects of short-term synaptic depression at thalamocortical synapses on orientation tuning in cat V1.
We examine the effects of short-term synaptic depression on the orientation tuning of the LGN input to simple cells in cat primary visual cortex (V1). The total LGN input has an untuned component as well as a tuned component, both of which grow with stimulus contrast. The untuned component is not visible in the firing rate responses of the simple cells. The suppression of the contribution of the untuned input component to firing rate responses is key to establishing orientation selectivity and its invariance with stimulus contrast. It has been argued that synaptic depression of LGN inputs could contribute to the selective suppression of the untuned component and thus contribute to the tuning observed in simple cells. We examine this using a model fit to the depression observed at thalamocortical synapses in-vivo, and compare this to an earlier model fit based on in-vitro observations. We examine the tuning of both the conductance and the firing rate induced in simple cells by the net LGN input. We find that depression causes minimal suppression of the untuned component. The primary effect of depression is to cause the contrast response curve to saturate at lower contrasts without differentially affecting the tuned vs. untuned components. This effect is slightly weaker for in-vivo vs. in-vitro parameters. Thus, synaptic depression of LGN inputs does not appreciably contribute to the orientation tuning of V1 simple cells.


Canonical Grading Scales of Corneal and Conjunctival Staining Based on Psychophysical and Physical Attributes.
In this study, we apply psychophysical scaling principles based on physical (photometric) attributes of images to better understand the factors involved in clinician judgement of ocular surface staining and, using that knowledge, to develop photographic scales for the assessment of staining for dry eye (DE) and related conditions. Subjects with noninfectious ocular surface staining were enrolled at five clinical sites. Following instillation of fluorescein, photographs of corneal staining were taken every 30 seconds for at least 5 minutes. The same procedure was followed for conjunctival staining after instillation of 2 µl of 1% lissamine green. A subset of the best corneal and bulbar conjunctival staining images were anonymized and a spectroradiometer measured photometric attributes (luminance and chromaticity). The images were scaled psychophysically by study investigators, who participated in constructing grading scales based on physical and psychophysical analyses. The final grading scales were refined following consultation with outside DE experts. Photographs were collected from 142 subjects (81% women), with an average age of 58 ± 17 years; 89% were diagnosed with DE. There was a monotonic relationship between between physical measurements and psychophysically scaled staining of both corneal (fluorescein) and bulbar (lissamine green) staining. Michelson contrast and u' (chromaticity) accounted for 66% and 64% of the variability in the psychophysically scaled images of fluorescein corneal and lissamine green conjunctival staining, respectively. This paper provides examples of the first ever clinically usable ocular surface staining scales validated using psychophysical scaling and the physical attributes (luminance and chromaticity) of the staining itself. In addition, it provides a generalizable method for the development of other clinical scales of ocular appearance.


Timing-invariant imaging of collateral vessels in acute ischemic stroke.
Although collateral vessels have been shown to be an important prognostic factor in acute ischemic stroke, patients with lack of collaterals on standard imaging techniques may still have good clinical outcome. We postulate that in these cases collateral vessels are present though not visible on standard imaging techniques that are based on a single time frame. This study included 40 consecutive patients with acute ischemic stroke with a large-vessel occlusion. Standard computed tomography angiography (CTA, single time frame) and CT perfusion (multiple time frames) were obtained at admission and timing-invariant (TI)-CTA was created from the CT perfusion data. Clinical outcome data (modified Rankin Scale) were assessed at 3-month follow-up. Four experienced observers independently assessed collateral status twice on both standard CTA and TI-CTA in an independent, blinded, randomized manner. Collateral status was rated as good if ≥50% and poor if <50% of collaterals were present compared with the contralateral hemisphere. Collateral status was rated higher on TI-CTA (good in 84%) compared with standard CTA (good in 49%; P<0.001). Thirty-one percent of patients with poor collateral status on standard CTA still had good clinical outcome. All of those patients, however, showed good collaterals on TI-CTA. All cases with poor collateral status rated on TI-CTA had poor clinical outcome. Collateral vessels may not always be visible on standard single time-frame CTA because of delayed contrast arrival. Future prognostic studies in acute stroke should consider delay-insensitive techniques, such as TI-CTA, instead of standard single time-frame imaging, such as standard CTA.


Actuarial Survival Based on Gestational Age in Days at Birth for Infants Born at <26 Weeks of Gestation.
To provide comprehensive, contemporary information on the actuarial survival of infants born at 22-25 weeks of gestation in Canada. In a retrospective cohort study, we included data from preterm infants of 22-25 weeks of gestation admitted to neonatal intensive care units participating in the Canadian Neonatal Network between 2010 and 2017. Infants with major congenital anomalies were excluded. We calculated gestational age using in vitro fertilization date, antenatal ultrasound dating, last menstrual period, obstetrical estimate, or neonatal estimate (in that order). Infants were followed until either discharge or death. Each day of gestational age was considered a category except for births at 22 weeks, where the first 4 days were grouped into one category and the last 3 days were grouped into another category. For each day of life, an actuarial survival rate was obtained by calculating how many infants survived to discharge out of those who had survived up to that day. Of 4335 included infants, 85, 679, 1504, and 2067 were born at 22, 23, 24, and 25 weeks of gestation, respectively. Survival increased from 32% at 22 weeks to 83% at 254-6/7 weeks. Graphs of actuarial survival developed for the first 6 weeks after birth in male and female children indicated a steep increase in survival during the first 7-10 days postnatally. Survival increased steadily with postnatal survival and was dependent on gestational age in days and sex of the child.


Cooperative signaling between Wnt1 and integrin-linked kinase induces accelerated breast tumor development.
Breast cancer is genetically and clinically a heterogeneous disease. However, the exact contribution of different cell types and oncogenic mutations to this heterogeneity are not well understood. Recently, we discovered an interaction between Wnt and integrin-linked kinase (ILK) within the signaling cascade that regulates cell growth and survival. Interestingly, mammary-specific expression of either one of these proteins has been shown to promote mammary tumorigenesis. In light of our recent findings and to investigate the potential interaction between Wnt and ILK proteins during mammary tumor formation and progression, we established a transgenic mouse model that expresses both Wnt and ILK in mammary epithelial cells. A novel transgenic mouse model with mammary-specific expression of both Wnt1 and ILK was generated by crossing the two previously characterized mouse models, MMTV-Wnt1 and MMTV-ILK. The resulting MMTV-Wnt/ILK mice were closely monitored for tumor development and growth, as well as for the tumor onset. The molecular phenotypes of both tumors and premalignant mammary glands were investigated by using biochemical and global gene-expression analysis approaches. A significant acceleration in mammary tumor incidence and growth was observed in the MMTV-Wnt/ILK mice. Pre-neoplastic mammary glands also display lobuloalveolar hyperplasia and an increase in ductal epithelium proliferation. Apart from elevated expression of Wnt/ILK targets, such as beta-catenin and cyclin D1, gene-expression profiling identified the surprising activation of the FOXA1 transcription factor. Upregulation of FOXA1, which is also known as the molecular marker of differentiated mammary luminal cells, was consistent with the expansion of the enriched luminal progenitor population or CD29loCD24hiCD61+ cells in MMTV-Wnt/ILK tumors. These results show cooperation between Wnt1 and ILK transgenes during mammary carcinogenesis, leading to changes in a transcriptional network, which could dictate a specific breast cancer phenotype with enhanced growth dynamics. The MMTV-Wnt/ILK can be used as a model to identify further the genes downstream of the estrogen receptor-beta/FOXA1 and to investigate the mechanisms targeting the expansion of the luminal progenitor cells leading to hyperplasia and tumorigenesis.


Kinematic determinants of human locomotion.
1. The aim of this study was to find kinematic patterns that are invariant across the normal range of locomotion speeds. Subjects walked at different, freely chosen speeds ranging from 0.9 to 2.1 m s-1, while motion and ground reaction forces on the right side of the body were recorded in three-dimensional space. 2. The time course of the anatomical angles of flexion-extension at the hip and ankle was variable not only across subjects, but even from trial to trial in the same subject. By contrast, the time course of the changes in the angles of elevation of each limb segment (pelvis, thigh, shank and foot) relative to the vertical was stereotyped across subjects. 3. To compare the waveforms across speeds, data were scaled in time relative to gait cycle duration. The pattern of ground reaction forces was highly speed dependent. Several distinct families of curves could be recognized in the flexion-extension angles at the hip and ankle. Instead, the waveforms of global length and elevation of the limb, elevation angles of all limb segments and flexion-extension at the knee were invariant with speed. 4. When gait trajectories at all speeds are plotted in the position space defined by the elevation angles of the limb segments, they describe regular loops on a plane. The statistical characteristics of these angular covariations were quantified by means of principal component analysis. The first two principal components accounted together for > 99% of the total experimental variance, and were quantitatively comparable in all subjects. 5. This constraint of planar covariation of the elevation angles is closely reminiscent of that previously described for the control of posture. The existence of laws of intersegmental co-ordination, common to the control of posture and locomotion, presumably assures the maintenance of dynamic equilibrium during forward progression, and the anticipatory adaptation to potentially destabilizing factors by means of co-ordinated kinematic synergies of the whole body.


[Clinical experience with 13 cases of orthotopic liver transplantation].
To review our experience with orthotopic liver transplantation. Thirteen liver transplantation were performed in 12 patients (including one liver retransplantation), of whom 5 patients received the transplantation for end stage liver cirrhosis, 4 for primary liver carcinoma, 1 for liver failure after hepatectomy for liver cancer, 1 for Wilson's disease, and 1 for chronic renal failure and liver cirrhosis. Retransplantation was done in 1 patient for chronic graft rejection. Of the 13 operations, 10 underwent the classical procedures of orthotopic liver transplantation, while 2 adopted modified piggyback technique, with 1 of the patients receiving retransplantation. Nine patients survived the transplantation with the longest survival over 2 years. Four patients died in the perioperative period, due to intracerebral bleeding, adult respiratory distress syndrome, acute renal failure and hepatic artery thrombus, respectively. Liver transplantation is an effective treatment for various end-stage liver diseases. Strict patient selection, appropriate timing of the operation and proper perioperative care are all essential for the success of liver transplantation.


Estrogen receptors differentially regulate intracellular calcium handling in human nonasthmatic and asthmatic airway smooth muscle cells.
Asthma is defined as chronic inflammation of the airways and is characterized by airway remodeling, hyperresponsiveness, and acute bronchoconstriction of airway smooth muscle (ASM) cells. Clinical findings suggest a higher incidence and severity of asthma in adult women, indicating a concrete role of sex steroids in modulating the airway tone. Estrogen, a major female sex steroid mediates its role through estrogen receptors (ER) ERα and ERβ, which are shown to be expressed in human ASM, and their expression is upregulated in lung inflammation and asthma. Previous studies suggested rapid, nongenomic signaling of estrogen via ERs reduces intracellular calcium ([Ca2+]i), thereby promoting relaxation of ASM. However, long-term ER activation on [Ca2+]i regulation in human ASM during inflammation or in asthma is still not known. In Fura-2-loaded nonasthmatic and asthmatic human ASM cells, we found that prolonged (24 h) exposure to ERα agonist (PPT) increased [Ca2+]i response to histamine, whereas ERβ activation (WAY) led to decreased [Ca2+] compared with vehicle. This was further confirmed by ER overexpression and knockdown studies using various bronchoconstrictor agents. Interestingly, ERβ activation was more effective than 17β-estradiol in reducing [Ca2+]i responses in the presence of TNF-α or IL-13, while no observable changes were noticed with PPT in the presence of either cytokine. The [Ca2+]i-reducing effects of ERβ were mediated partially via L-type calcium channel inhibition and increased Ca2+ sequestration by sarcoplasmic reticulum. Overall, these data highlight the differential signaling of ERα and ERβ in ASM during inflammation. Specific ERβ activation reduces [Ca2+]i in the inflamed ASM cells and is likely to play a crucial role in regulating ASM contractility, thereby relaxing airways.


Central CRF inhibits gastric emptying of a nutrient solid meal in rats: the role of CRF2 receptors.
Corticotropin-releasing factor (CRF)-related peptides exhibit different affinity for the receptor subtypes 1 and 2 cloned in the rat brain. We investigated, in conscious rats, the effects of intracisternal (i.c.) injection of CRF (rat/human) on the 5-h rate of gastric emptying of a solid nutrient meal (Purina chow and water ad libitum for 3 h) and the CRF receptor subtype involved. CRF, urotensin I (suckerfish), and sauvagine (frog) injected i.c. inhibited gastric emptying in a dose-dependent manner, with ED50 values of 0.31, 0.13, and 0.08 microgram/rat, respectively. Rat CRF-(6-33) (0.1-10 micrograms i.c.) had no effect. The nonselective CRF1 and CRF2 receptor antagonist, astressin, injected i.c. completely blocked the inhibitory effect of i.c. CRF, urotensin I, and sauvagine with antagonist-to-agonist ratios of 3:1, 10:1, and 16:1, respectively. The CRF1-selective receptor antagonist NBI-27914 injected i.c. at a ratio of 170:1 had no effect. These data show that central CRF and CRF-related peptides are potent inhibitors of gastric emptying of a solid meal with a rank order of potency characteristic of the CRF2 receptor subtype affinity (sauvagine > urotensin I > CRF). In addition, the reversal by astressin but not by the CRF1-selective receptor antagonist further supports the view that the CRF2 receptor subtype is primarily involved in central CRF-induced delayed gastric emptying.


Bayesian Surprise Predicts Human Event Segmentation in Story Listening.
Event segmentation theory posits that people segment continuous experience into discrete events and that event boundaries occur when there are large transient increases in prediction error. Here, we set out to test this theory in the context of story listening, by using a deep learning language model (GPT-2) to compute the predicted probability distribution of the next word, at each point in the story. For three stories, we used the probability distributions generated by GPT-2 to compute the time series of prediction error. We also asked participants to listen to these stories while marking event boundaries. We used regression models to relate the GPT-2 measures to the human segmentation data. We found that event boundaries are associated with transient increases in Bayesian surprise but not with a simpler measure of prediction error (surprisal) that tracks, for each word in the story, how strongly that word was predicted at the previous time point. These results support the hypothesis that prediction error serves as a control mechanism governing event segmentation and point to important differences between operational definitions of prediction error.


Automatic diagnosis of true proximity between the mandibular canal and the third molar on panoramic radiographs using deep learning.
Evaluating the mandibular canal proximity is crucial for planning mandibular third molar extractions. Panoramic radiography is commonly used for radiological examinations before third molar extraction but has limitations in assessing the true contact relationship between the third molars and the mandibular canal. Therefore, the true relationship between the mandibular canal and molars can be determined only through additional cone-beam computed tomography (CBCT) imaging. In this study, we aimed to develop an automatic diagnosis method based on a deep learning model that can determine the true proximity between the mandibular canal and third molars using only panoramic radiographs. A total of 901 third molars shown on panoramic radiographs were examined with CBCT imaging to ascertain whether true proximity existed between the mandibular canal and the third molar by two radiologists (450 molars: true contact, 451 molars: true non-contact). Three deep learning models (RetinaNet, YOLOv3, and EfficientDet) were developed, with performance metrics of accuracy, sensitivity, and specificity. EfficientDet showed the highest performance, with an accuracy of 78.65%, sensitivity of 82.02%, and specificity of 75.28%. The proposed deep learning method can be helpful when clinicians must evaluate the proximity of the mandibular canal and a third molar using only panoramic radiographs without CBCT.


[Hermaphrodites and intersexed individuals from myth to reality. Second part].
It was not until the nineteenth century that the heavy repressive measures usually taken against intersexed individuals were somewhat alleviated and a genuinely scientific approach to intersexuality began to be promoted. A first step was the application of the concept of pseudo-hermaphroditism to cases in which the external and/or internal sexual organs did not correspond to the gonadal sex. Through experimental application of the bovine freemartin model, the role of male hormones in embryonic sexual differentiation was able to be elucidated. Consequently, modern endocrinology has contributed significantly to the understanding of various types of intersexuality such as, for instance, the female adreno-genital syndrome and peripheral tissue insensitivity to androgens. Finally, chromosomal and molecular genetics have enabled the localisation of the genes responsible for sexual differentiation and allowed an understanding of the different causes of intersexed cases belonging to the vast chapter of gonadal dysgnesis. Some associations of patients are currently questioning medical and surgical treatments which aim at the production of strict sexual differentiation in morphologically ambiguous individuals.


Silencing of NtMPK4 impairs CO-induced stomatal closure, activation of anion channels and cytosolic Casignals in Nicotiana tabacum guard cells.
Light-induced stomatal opening in C3 and C4 plants is mediated by two signalling pathways. One pathway is specific for blue light and involves phototropins, while the second pathway depends on photosyntheticaly active radiation (PAR). Here, the role of NtMPK4 in light-induced stomatal opening was studied, as silencing of this MAP kinase stimulates stomatal opening. Stomata of NtMPK4-silenced plants do not close in elevated atmospheric CO(2), and show a reduced response to PAR. However, stomatal closure can still be induced by abscisic acid. Measurements using multi-barrelled intracellular micro-electrodes showed that CO(2) activates plasma membrane anion channels in wild-type Nicotiana tabacum guard cells, but not in NtMPK4-silenced cells. Anion channels were also activated in wild-type guard cells after switching off PAR. In approximately half of these cells, activation of anion channels was accompanied by an increase in the cytosolic free Ca(2+) concentration. The activity of anion channels was higher in cells showing a parallel increase in cytosolic Ca(2+) than in those with steady Ca(2+) levels. Both the darkness-induced anion channel activation and Ca(2+) signals were repressed in NtMPK4-silenced guard cells. These data show that CO(2) and darkness can activate anion channels in a Ca(2+)-independent manner, but the anion channel activity is enhanced by parallel increases in the cytosolic Ca(2+) concentration. NtMPK4 plays an essential role in CO(2)- and darkness-induced activation of guard-cell anion channels, through Ca(2+)-independent as well as Ca(2+)-dependent signalling pathways.


Application of numerical simulation on optimum design of two-dimensional sedimentation tanks in the wastewater treatment plant.
The paper establishes the relationship between the settling efficiency and the sizes of the sedimentation tank through the process of numerical simulation, which is taken as one of the constraints to set up a simple optimum designing model of sedimentation tank. The feasibility and advantages of this model based on numerical calculation are verified through the application of practical case.


Maternal and birth attendant hand washing and neonatal mortality in southern Nepal.
More than 95% of neonatal deaths occur in developing countries, approximately 50% at home. Few data are available on the impact of hand-washing practices by birth attendants or caretakers on neonatal mortality. To evaluate the relationship between birth attendant and maternal hand-washing practices and neonatal mortality in rural Nepal. Observational prospective cohort study. Sarlahi District in rural southern Nepal. Newborn infants were originally enrolled in a community-based trial assessing the effect of skin and/or umbilical cord cleansing with chlorhexidine on neonatal mortality in southern Nepal. A total of 23,662 newborns were enrolled and observed through 28 days of life. Questionnaires were administered to mothers on days 1 and 14 after delivery to identify care practices and risk factors for mortality and infection. Three hand-washing categories were defined: (1) birth attendant hand washing with soap and water before assisting with delivery, (2) maternal hand washing with soap and water or antiseptic before handling the baby, and (3) combined birth attendant and maternal hand washing. Mortality within the neonatal period. Birth attendant hand washing was related to a statistically significant lower mortality rate among neonates (adjusted relative risk [RR] = 0.81; 95% confidence interval [CI], 0.66-0.99), as was maternal hand washing (adjusted RR = 0.56; 95% CI, 0.38-0.82). There was a 41% lower mortality rate among neonates exposed to both hand-washing practices (adjusted RR = 0.59; 95% CI, 0.37-0.94). Birth attendant and maternal hand washing with soap and water were associated with significantly lower rates of neonatal mortality. Measures to improve or promote birth attendant and maternal hand washing could improve neonatal survival rates.


NANOG Restores Contractility of Mesenchymal Stem Cell-Based Senescent Microtissues.
Mesenchymal stem cells (MSCs) have been extensively used in the field of tissue engineering as a source of smooth muscle cells (SMCs). However, recent studies showed deficits in the contractile function of SMCs derived from senescent MSCs and there are no available strategies to restore the contractile function that is impaired due to cellular or organismal senescence. In this study, we developed a tetracycline-regulatable system and employed micropost tissue arrays to evaluate the effects of the embryonic transcription factor, NANOG, on the contractility of senescent MSCs. Using this system, we show that expression of NANOG fortified the actin cytoskeleton and restored contractile function that was impaired in senescent MSCs. NANOG increased the expression of smooth muscle α-actin (ACTA2) as well as the contractile force generated by cells in three-dimensional microtissues. Interestingly, NANOG worked together with transforming growth factor-beta1 to further enhance the contractility of senescent microtissues. The effect of NANOG on contractile function was sustained for about 10 days after termination of its expression. Our results show that NANOG could reverse the effects of stem cell senescence and restore the myogenic differentiation potential of senescent MSCs. These findings may enable development of novel strategies to restore the function of senescent cardiovascular and other SMC-containing tissues.


ATF4-dependent fructolysis fuels growth of glioblastoma multiforme.
Excessive consumption of fructose in the Western diet contributes to cancer development. However, it is still unclear how cancer cells coordinate glucose and fructose metabolism during tumor malignant progression. We demonstrate here that glioblastoma multiforme (GBM) cells switch their energy supply from glycolysis to fructolysis in response to glucose deprivation. Mechanistically, glucose deprivation induces expression of two essential fructolytic proteins GLUT5 and ALDOB through selectively activating translation of activating transcription factor 4 (ATF4). Functionally, genetic or pharmacological disruption of ATF4-dependent fructolysis significantly inhibits growth and colony formation of GBM cells in vitro and GBM growth in vivo. In addition, ATF4, GLUT5, and ALDOB levels positively correlate with each other in GBM specimens and are poor prognostic indicators in GBM patients. This work highlights ATF4-dependent fructolysis as a metabolic feature and a potential therapeutic target for GBM.


The spatial scale of attention strongly modulates saccade latencies.
We have previously shown that when a stimulus consisting of two concentric rings moves, saccade latencies are much longer (by 150 ms) when attention is directed to the larger ring than to the smaller ring. Here, we investigated whether this effect can be explained by a deferral of the "cost" of making a saccade while the target remains inside the attentional field, or by purely visual factors (eccentricity or contrast). We found 1) latencies were shorter when attention was directed to small features irrespective of retinal eccentricity; 2) saccade latency distributions were systematically determined by the ratio between the amplitude of the stimulus step and the diameter of the attended ring: stimulus steps that were larger than the attended ring resulted in short latencies, whereas steps smaller than the attended ring resulted in proportionally longer and more variable latencies; 3) this effect was not seen in manual reaction times to the same target movement; and 4) suprathreshold changes in the contrast of targets, mimicking possible attentional effects on perceived contrast and saliency, had little effect on latency. We argue that the spatial scale of attention determines the urgency of saccade motor preparation processes by changing the rate and rate variability of the underlying decision signal, to defer the cost of saccades that result in little visual benefit.


Chromosome markers in Mus musculus: strain differences in C-banding.
The mitotic chromosomes of several inbred strains of mice and a series of F(1) hybrids have been analyzed by quinacrine staining and further characterized by the centromeric heterochromatin banding (C-banding). Inbred strains had the same amount of C-banding material on homologous chromosomes but showed variation in the amount on different chromosomes. F(1) hybrids showed characteristics of each parent and it appears that the amount of C-banding on each chromosome is a simple inherited polymorphism. In this study 12 different chromosomes could be distinguished by their C-banding, and these can be used as normal chromosome markers.


Safety and tolerability of 6-month supplementation with a vitamin D, calcium and leucine-enriched whey protein medical nutrition drink in sarcopenic older adults.
Safety and tolerability of prolonged supplementation with a vitamin D, calcium and leucine-enriched whey protein medical nutrition drink (WP-MND) was evaluated in sarcopenic older adults. A 13-week double-blinded, randomized, isocaloric placebo-controlled trial (PROVIDE study; n = 380) was extended with a voluntary 13-week open-label extension (OLE). OLE participants were randomized to receive daily 1 or 2 servings of WP-MND (21 g protein, 3 g leucine, 10 µg vitD and 500 mg calcium per serving). Gastro-intestinal tolerability, kidney function and serum levels of calcidiol, parathyroid hormone (PTH) and calcium were evaluated at week 0, 13 and 26. In response to the high daily protein intake (median1.5; IQR: 1.3, 1.7 g/kg BW/day), the estimated glomerular filtration rate (eGFR) increased in the test group during the RCT (p = 0.013). The same trend was observed for those participants with moderate chronic kidney disease. During OLE no eGFR change was observed in any of the groups. Serum calcidiol and calcium reached a plateau after 13-week WP-MND supplementation. As expected, PTH significantly changed in the opposite direction, decreasing during RCT in the test group (T vs C: p < 0.001) and during OLE in former control groups. During RCT, 20/366 participants with normal baseline calcidiol reached levels ≥ 100 nmol/L (T: n = 18; C: n = 2) and 6 developed albumin-corrected calcium levels > 2.55 mmol/L (T: n = 3; C: n = 3), without associated adverse events. A 6 months intervention with up to 2 servings of WP-MND did neither result in kidney function deterioration nor symptoms of vitamin D or calcium toxicity. The product was overall well tolerated.


Genetic diversity and drug sensitivity profile of Mycobacterium tuberculosis among children in Ethiopia.
Worldwide, tuberculosis (TB) affects about one million children every year. The burden of the disease is higher in developing countries. However, there is limited information on the lineages and drug sensitivity patterns of Mycobacterium tuberculosis (M. tuberculosis) infecting children in these countries, including Ethiopia. Thus, this study aimed to characterize the different lineages of the M. tuberculosis complex causing childhood pulmonary tuberculosis and evaluate the drug-sensitivity patterns to the first-line anti-TB drugs. A total of 54 stored cultures were used in this study. The region of difference 9 (RD9) based polymerase chain reaction (PCR) and spoligotyping were employed for the identification of the isolates at the species and lineages level respectively. Lineage identification was done by using the pre-existing database. Identification of clustering of the spoligotype patterns was by using the SPOLIDB3-based model. The result was retrieved by the most probable family format. Furthermore, the phenotypic, and genotypic drug-sensitivity test (DST) was performed using Mycobacterium Growth Indicator Tube (MGIT™ 960) and GenoTypeMTBDRplus assay respectively. Data analysis was done using SPSS version 27 software. Spoligotyping produced 39 interpretable results for M. tuberculosis. The majority (74.4%) of them were clustered into 7 groups, while the rest (25.6%) were single. The Euro-American (EA) lineage was the predominant lineage (64.1%) followed by the East-African Indian (EAI) (30.8%) and M. Africanum (5.1%) lineages. The most predominant subtypes were SIT37 (15.4%), SIT149 (12.8%), SIT25 (7.7%), and SIT53 (7.7%). Furthermore, of the identified SITs, T1 and CAS families consisted of 38.5% and 28.2% of the lineages respectively. Drug susceptibility was 91.9% by phenotypic method and 97.4% by molecular assay. The overall prevalence of any resistance was 7.8% and there was a single MDR-TB. Many of the isolates belong to the modern lineages (Euro American) representing the most common circulating strains in the country. More importantly, despites the tiny isolates tested, drug resistance is low. To fully describe the molecular epidemiology of MTBC lineages in children, we recommend a prospective large-scale study.


Ketone body and fatty acid metabolism in sheep tissues. 3-Hydroxybutyrate dehydrogenase, a cytoplasmic enzyme in sheep liver and kidney.
1. 3-Hydroxybutyrate dehydrogenase (EC 188.8.131.52) activities in sheep kidney cortex, rumen epithelium, skeletal muscle, brain, heart and liver were 177, 41, 38, 33, 27 and 17mumol/h per g of tissue respectively, and in rat liver and kidney cortex the values were 1150 and 170 respectively. 2. In sheep liver and kidney cortex the 3-hydroxybutyrate dehydrogenase was located predominantly in the cytosol fractions. In contrast, the enzyme was found in the mitochondria in rat liver and kidney cortex. 3. Laurate, myristate, palmitate and stearate were not oxidized by sheep liver mitochondria, whereas the l-carnitine esters were oxidized at appreciable rates. The free acids were readily oxidized by rat liver mitochondria. 4. During oxidation of palmitoyl-l-carnitine by sheep liver mitochondria, acetoacetate production accounted for 63% of the oxygen uptake. No 3-hydroxybutyrate was formed, even after 10min anaerobic incubation, except when sheep liver cytosol was added. With rat liver mitochondria, half of the preformed acetoacetate was converted into 3-hydroxybutyrate after anaerobic incubation. 5. Measurement of ketone bodies by using specific enzymic methods (Williamson, Mellanby & Krebs, 1962) showed that blood of normal sheep and cattle has a high [3-hydroxybutyrate]/[acetoacetate] ratio, in contrast with that of non-ruminants (rats and pigeons). This ratio in the blood of lambs was similar to that of non-ruminants. The ratio in sheep blood decreased on starvation and rose again on re-feeding. 6. The physiological implications of the low activity of 3-hydroxybutyrate dehydrogenase in sheep liver and the fact that it is found in the cytoplasm in sheep liver and kidney cortex are discussed.


Deep transfer learning-based anomaly detection for cycling safety.
Despite the general improvements in road safety, with the growing number of bicycle users, cycling safety is still a challenge as demonstrated by the fact that it is the only road transport mode with an increase in the number of fatalities in EU cities. Moreover, to analyze the problem to improve the road transport system, the traditional network screening based on crash statistics is a reactive approach and less effective due to the lack of suitable bicycle data availability, as well. In such a framework, new opportunities for data collection in smart cities and communities are emerging as proactive approaches to identify critical locations where safety treatments can be effectively applied to prevent bicycle crashes. This research applied a deep transfer learning model to detect anomalies in cycling behavior that can be associated with traffic conflicts or near-miss crashes. The paper presents how to build a users' tailored riding model named DTL AD to detect and localize riding anomalies by using a set of data in the National Marine Electronics Association (NMEA) string of Global Navigation Satellite System (GNSS) recorded with instrumented bicycles by different cyclists. More specifically, DTL AD exploits a convolutional autoencoder (CAE) with transfer learning to reduce data labelling and training effort. A case study demonstrates the identification of anomalies in cycling behavior visually represented on Geographic Information Systems (GIS) maps, showing how data clustering is well located in high-risk areas.


Design of signal-adapted multidimensional lifting scheme for lossy coding.
This paper proposes a new method for the design of lifting filters to compute a multidimensional nonseparable wavelet transform. Our approach is stated in the general case, and is illustrated for the 2-D separable and for the quincunx images. Results are shown for the JPEG2000 database and for satellite images acquired on a quincunx sampling grid. The design of efficient quincunx filters is a difficult challenge which has already been addressed for specific cases. Our approach enables the design of less expensive filters adapted to the signal statistics to enhance the compression efficiency in a more general case. It is based on a two-step lifting scheme and joins the lifting theory with Wiener's optimization. The prediction step is designed in order to minimize the variance of the signal, and the update step is designed in order to minimize a reconstruction error. Application for lossy compression shows the performances of the method.


Molecular and descriptive epidemiologyof multidrug-resistant Enterobacteriaceae in hospitalized infants.
To investigate the epidemiology of multidrug-resistant Enterobacteriaceae (MDRE) in hospitalized infants. From 2000 through 2005, active surveillance cultures for MDRE were performed for patients admitted to a 40-bed neonatal intensive care unit (NICU) that provides care for critically ill infants 6 months of age or younger. MDRE epidemiology and the genetic relatedness of MDRE strains determined by repetitive-sequence polymerase chain reaction were analyzed. Active surveillance cultures revealed that 759 (23%) of 3,370 NICU infants (or approximately 1 in 5) developed MDRE colonization or infection and that 613 (72%) of the 853 isolates with epidemiologic data available were healthcare acquired. MDRE colonization occurred more frequently (in 653 infants [86%]) than did MDRE infection (in 106 [14%]). Of the 653 infants with MDRE colonization, 119 (18%) eventually became infected, with 29 (4%) acquiring sterile site infections. The most commonly isolated organisms were the Enterobacter species, accounting for 612 (71%) of the 862 isolates. Molecular epidemiologic analysis revealed that genetic-relatedness clustering (related clusters defined as having a genetic similarity coefficient greater than 95%) varied depending on microbial species. Clustering was detected for 36 (78%) of the 46 Enterobacter aerogenes isolates, 22 (45%) of the 49 Enterobacter cloacae isolates, and 13 (59%) of the 22 Klebsiella pneumoniae isolates. Hospitalized infants are at significant risk of acquiring MDRE, specifically Enterobacter species, at the study institution. Active surveillance cultures identified colonized patients who likely contributed to the institutional reservoir of MDRE. Molecular epidemiologic studies suggest that both patient-to-patient transmission and de novo acquisition of resistance play a role in the acquisition of these organisms, and that the clinical significance of such acquisition varies by species. The high percentage of E. aerogenes isolates that demonstrated genetic clustering suggests that monitoring the prevalence of this organism could serve as a useful measure of compliance with infection control procedures.


Late onset immunodeficiency in a patient with recurrent thymic carcinoma and myasthenia gravis.
The most common autoimmune disease associated with thymoma is myasthenia gravis. In addition, cellular and humoral immune defects have been frequently reported in association with thymic neoplasms. Here we report the case of a patient with myasthenia gravis receiving long-term immunosuppression with azathioprine and recurrent well-differentiated thymic carcinoma who developed CD4+ T-cell depletion and CNS cryptococcosis after multiple courses of chemotherapy and mediastinal irradiation. We hypothesize that in thymectomized patients bone marrow suppression and abrogation of the peripheral T-cell pool can result in a delayed T-cell regeneration due to the lack of functional thymic epithelium.


Cyclophilin D disruption attenuates lipopolysaccharide-induced inflammatory response in primary mouse macrophages.
According to recent results, various mitochondrial processes can actively regulate the immune response. In the present report, we studied whether mitochondrial permeability transition (mPT) has such a role. To this end, we compared bacterial lipopolysaccharide (LPS)-induced inflammatory response in cyclophilin D (CypD) knock-out and wild-type mouse resident peritoneal macrophages. CypD is a regulator of mPT; therefore, mPT is damaged in CypD(-/-) cells. We chose this genetic modification-based model because the mPT inhibitor cyclosporine A regulates inflammatory processes by several pathways unrelated to the mitochondria. The LPS increased mitochondrial depolarisation, cellular and mitochondrial reactive oxygen species production, nuclear factor-κB activation, and nitrite- and tumour necrosis factor α accumulation in wild-type cells, but these changes were diminished or absent in the CypD-deficient macrophages. Additionally, LPS enhanced Akt phosphorylation/activation as well as FOXO1 and FOXO3a phosphorylation/inactivation both in wild-type and CypD(-/-) cells. However, Akt and FOXO phosphorylation was significantly more pronounced in CypD-deficient compared to wild-type macrophages. These results provide the first pieces of experimental evidence for the functional regulatory role of mPT in the LPS-induced early inflammatory response of macrophages.


Notch and its oncogenic activity in human malignancies.
Increasing evidence has demonstrated that Notch signaling is deregulated in human hematological malignancies and solid tumors. This signaling has a protumorigenic effect but may also act as a tumor suppressor. How induction of a single pathway gives rise to the opposite effects in different cell types is still unknown. This review article includes available data from peer-reviewed publications associated with the role of Notch signaling during cancer pathogenesis. Numerous reports have indicated that alterations in Notch signaling and its oncogenic activity were originally associated with the pathogenesis of T‑cell acute lymphoblastic leukemia/lymphoma (T-ALL), an aggressive hematologic tumor affecting children and adolescents. The possibility that Notch could play a significant role in human breast cancer development comes from studies on mouse mammary tumor virus-induced cancer. Numerous findings over the past several years have indicated that alterations in Notch signaling are also responsible for ovarian cancer development. Mention should also be made of the connection between expression of Notch 3 and increased resistance to chemotherapy, which remains a major obstacle to successful treatment. Notch as an oncogenic factor is also involved in the development of colon cancer, lung carcinoma and Kaposi's sarcoma. Notch is a binary cell fate determinant and its overexpression has been described as oncogenic in a wide array of human malignancies. This finding led to interest in therapeutically targeting this pathway, especially by the use of gamma-secretase inhibitors (GSIs) blocking the cleavage of Notch receptors at the cell membrane by the inhibition of Notch intracellular domain (NICD) releasing. Preclinical cancer models have revealed that GSIs suppress the growth of cancers such as pancreatic, breast and lung cancer.


Prospects for sustainability of pig production in relation to climate change and novel feed resources.
Pig production systems provide multiple benefits to humans. However, the global increase in meat consumption has profound consequences for our earth. This perspective describes two alternative scenarios for improving the sustainability of future pig production systems. The first scenario is a high input-high output system based on sustainable intensification, maximizing animal protein production efficiency on a limited land surface at the same time as minimizing environmental impacts. The second scenario is a reduced input-reduced output system based on selecting animals that are more robust to climate change and are better adapted to transform low quality feed (local feeds, feedstuff co-products, food waste) into meat. However, in contrast to the first scenario, the latter scenario results in reduced predicted yields, reduced production efficiency and possibly increased costs to the consumer. National evaluation of the availability of local feed and feedstuff co-product alternatives, determination of limits to feed sourced from international markets, available land for crop and livestock production, desired production levels, and a willingness to politically enforce policies through subsidies and/or penalties are some of the considerations to combine these two scenarios. Given future novel sustainable alternatives to livestock animal protein, it may become reasonable to move towards an added general premium price on 'protein from livestock animals' to the benefit of promoting higher incomes to farmers at the same time as covering the extra costs of, politically enforced, welfare of livestock animals in sustainable production systems. © 2020 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Accumulation of LamB-LacZ hybrid proteins in intracytoplasmic membrane-like structures in Escherichia coli K12.
The subcellular location of LamB-LacZ hybrid proteins in the Escherichia coli K12 strains pop3234 and pop3299 was investigated by immunocytochemical detection and protease-accessibility experiments. Induction of the synthesis of the hybrid proteins resulted in the appearance of membrane-like structures within the cytoplasm of the cells. Labelling of ultrathin cryosections of the cells with anti-beta-galactosidase or anti-LamB protein serum and protein-A-gold complexes revealed that the hybrid proteins were associated with these membrane-like structures or accumulated within the cytoplasm. Protease-accessibility experiments confirmed this localization. Moreover, when low quantities of hybrid proteins were produced, i.e. in uninduced pop3234 cells or in induced pop3299 cells, the hybrid proteins were accessible to trypsin from the periplasmic side of the inner membrane, leaving protected fragments with an apparent Mr of 83,000. Apparently, these hybrid proteins are partly translocated through the inner membrane, resulting in membrane-spanning forms of the proteins.


Survival and cause of death in multiple sclerosis: a prospective population-based study.
Detailed studies of mortality in multiple sclerosis (MS) are limited. Studying death certificates in a prospective cohort of patients known to have MS is of value in establishing mortality data and can also provide important information on the accuracy and use of death certificates for epidemiological studies. A population-based survey performed in South Wales in 1985 identified 441 patients. Cases were flagged with the Office of Population Censuses and Surveys and death certificates collected prospectively for more than 20 years. Median observed survival time was 38.0 years from symptom onset. Mean age at death was 65.3 for women and 65.2 years for men. Mean age at death in patients dying from MS-related causes was 62.5 and 69.3 years (p<0.001) for unrelated deaths. Those dying of MS-related causes had a younger age at disease onset (32.5) compared with those dying of unrelated causes (36.8 years) (p = 0.01). Cause of death was related to MS in 57.9% and unrelated in 42.1% of individuals. In 27% of patients, "MS" was absent from the death certificate. The most common cause of death was respiratory disease (47.5%). The standardised mortality ratio was 2.79 (95% CI 2.44 to 3.18) so that MS patients were almost three times more likely to die prematurely relative to the general population. These results confirm a continuing trend of premature death in patients with MS. Relying on data derived from death certificates will underestimate disease prevalence. Differences were identified between those dying from MS-related causes and those dying from other causes.


Linear superposition electrical impedance tomography imaging with multiple electrical/biopsy probes.
In medical diagnostics, tissue is often examined with multiple discrete biopsies taken under ultrasound placement. In a previous theoretical study, we have suggested that the linear nature of the equations used in electrical impedance tomography (EIT) can be employed with the conventional practice of biopsy sampling to produce an image of the tissue between the biopsy samplings. Specifically, the biopsy probes can be used to record EIT-type electrical data during the discrete tissue sampling. The location of the discrete biopsy needle insertions available from the ultrasound placement of the probes can be combined with the electrical measurement data and used with linear superposition to produce a complete EIT image of the tissue between the sampled sites. In this study, we explore the concept experimentally using gel phantoms to simulate tissue and heterogeneities in the tissue. The experiments are performed in 2-D and 3-D configurations, and data are taken discretely, one at a time, through single electrical probe insertions. In the 2-D configuration, we were able to produce images of reasonable quality for heterogeneities with a diameter larger than 3 mm (conductivity ratio 1:5) and with relative conductivity differences above 50% (diameter 5 mm).


Mutations affecting beta-tubulin folding and degradation.
Revertants of a colcemid-resistant Chinese hamster ovary cell line with an altered (D45Y) beta-tubulin have allowed the identification of four cis-acting mutations (L187R, Y398C, a 12-amino acid in-frame deletion, and a C-terminal truncation) that act by destabilizing the mutant tubulin and preventing it from incorporating into microtubules. These unstable beta-tubulins fail to form heterodimers and are predominantly found in association with the chaperonin CCT, suggesting that they cannot undergo productive folding. In agreement with these in vivo observations, we show that the defective beta-tubulins do not stably interact with cofactors involved in the tubulin folding pathway and, hence, fail to exchange with beta-tubulin in purified alphabeta heterodimers. Treatment of cells with MG132 causes an accumulation of the aberrant tubulins, indicating that improperly folded beta-tubulin is degraded by the proteasome. Rapid degradation of the mutant tubulin does not elicit compensatory changes in wild-type tubulin synthesis or assembly. Instead, loss of beta-tubulin from the mutant allele causes a 30-40% decrease in cellular tubulin content with no obvious effect on cell growth or survival.


[The immune system and its regulatory role in the processes of proliferation and differentiation in the body].
The reported and original research data on immune regulation of cellular proliferation and differentiation in diverse tissues are summarized. Such regulative function is considered to be the expression of the proposed role of the immune system in the realization of genetic information at the integral bodily level. It is postulated that in addition to the information flow: DNA--RNA--protein (in each cell), another information flow may exist: the central organs of the lymphoid system--lymphocytes migrating to different organs and tissues--organs and tissues characterized by specific organ, tissue and differentiation antigens.


Higher Mortality and Survival Benefit in Obese Patients Awaiting Liver Transplantation.
Over 85% of US centers adhere to practice guidelines that consider morbid obesity to be a contraindication to liver transplantation (LT). The relationship of morbid obesity with LT outcomes and survival benefit in the current era is unknown. We investigated the association of body mass index with waitlist and post-LT outcomes, and survival benefit, using the United Network for Organ Sharing registry. We categorized body mass index as follows: 18.5 to 29.9 kg/m, normal/overweight; 30 to 34.9 kg/m, obese; 35 to 39.9 kg/m, severely obese; and ≥40 kg/m, morbidly obese, and evaluated waitlist outcomes using competing risk regression and post-LT outcomes and survival benefit using Cox regression. 3.9% of 80 221 waitlisted and 3.5% of 38 177 transplanted patients were morbidly obese. Waitlist mortality was higher for morbidly obese than normal/overweight patients (subdistribution hazard ratio, 1.16; 95% confidence interval [CI]:1.08-1.26), but post-LT mortality and graft failure were comparable (hazard ratio [HR], 1.01; 95% CI, 0.86-1.19; and HR, 1.15; 95% CI, 0.95-1.40). Morbidly obese patients also benefited more from LT (88% mortality reduction vs 80% for normal/overweight). Morbid obesity predicted higher post-LT mortality before 2007 (HR, 1.18; 95% CI, 1.04-1.34), but not afterward (HR, 0.98; 95% CI, 0.81-1.18). Morbid obesity is associated with higher mortality on the LT waitlist, but no longer predicts inferior outcomes after LT. Morbidly obese patients should be considered potential candidates for LT.